Precision recharging of sorbent materials using patient and session data

ABSTRACT

The invention relates to devices, systems, and methods for recharging zirconium phosphate and/or zirconium oxide in reusable sorbent modules. The devices, systems, and methods provide for precision recharging of the zirconium phosphate and/or zirconium oxide to avoid the need of excess recharge solutions. The devices systems and methods also provide for calculation of the volumes of recharge solution needed for fully recharging the zirconium phosphate and zirconium oxide modules.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of U.S. patentapplication Ser. No. 15/364,251 filed Nov. 29, 2016, now U.S. Pat. No.10,159,957, which is a continuation-in-part application of U.S. patentapplication Ser. No. 14/722,119 filed May 26, 2015 now U.S. Pat. No.10,052,612, and U.S. patent application Ser. No. 14/722,068 filed May26, 2015, now U.S. Pat. No. 9,981,245. U.S. patent application Ser. No.14/722,119 and U.S. patent application Ser. No. 14/722,068 are eachcontinuation-in-part applications of U.S. patent application Ser. No.14/261,651 filed Apr. 25, 2014, now U.S. Pat. No. 9,895,477, and U.S.patent application Ser. No. 14/642,847 filed Mar. 20, 2015, now U.S.Pat. No. 9,974,896. U.S. patent application Ser. No. 14/261,651 plainsthe benefit of and priority to U.S. Provisional Patent Application No.61/941,672 filed Feb. 19, 2014 and U.S. Provisional Patent ApplicationNo. 61/909,372 filed Nov. 26, 2013. U.S. patent application Ser. No.14/642,847 claims the benefit of and priority to U.S. Provisional PatentApplication No. 62/016,613 filed Jun. 24, 2014 and U.S. ProvisionalPatent Application No. 62/077,159 filed Nov. 7, 2014.

FIELD OF THE INVENTION

The invention relates to devices, systems, and methods for rechargingzirconium phosphate and/or zirconium oxide in reusable sorbent modules.The devices, systems, and methods provide for precision recharging ofthe zirconium phosphate and/or zirconium oxide to avoid the need ofexcess recharge solutions. The devices systems and methods also providefor calculation of the volumes of recharge solution needed for fullyrecharging the zirconium phosphate and zirconium oxide modules.

BACKGROUND

Zirconium phosphate is used in sorbent dialysis to remove waste andunwanted solutes including ammonium, potassium, calcium, and magnesiumions from dialysate. Zirconium oxide can be used to remove phosphateions from dialysate. The zirconium phosphate and zirconium oxide aregenerally packaged in a sorbent cartridge. Usually, sorbent cartridgesare discarded and replaced after use. The discarded sorbent cartridgesare broken down and the zirconium phosphate and zirconium oxide areseparated from the other sorbent materials. Because zirconium phosphateand zirconium oxide are expensive and rechargeable, sorbentre-processors treat the recovered materials with chemical solutions. Therecycling process requires transporting the materials to reprocessingfacilities and involves laborious recycling steps in addition torecharging the sorbent materials. Further, the sorbent material cannotbe immediately reused, and must be added to a new sorbent cartridge andrepackaged for sale. Conventional methods drive up costs andinfrastructure requirements, and increase complexity and waste.

Different patients may require differing dialysate bicarbonate levelsfor effective treatment. For example, alkalotic patients require adialysate bicarbonate level lower than other patients. The bicarbonatelevel of the dialysate is generally controlled by the addition sodiumbicarbonate, which acts as a buffer. Bicarbonate ions in the dialysateare in equilibrium with carbon dioxide. The zirconium phosphate effluentpH is the main driver in determining the bicarbonate/carbon dioxideratio. A lower zirconium phosphate effluent pH will produce more pCO₂which can result in dialysate entering the dialyzer at too low a pH,potentially causing hemolysis. High pCO₂ can also cause bubbles to formin the dialysate which can potentially be transferred to the patient.The excess CO₂ can be removed by a degasser, such as a membranecontactor degasser, a vacuum degasser, or any other device capable ofremoving CO₂ from solution. A higher zirconium phosphate effluent pHwill result in higher bicarbonate concentration, requiring lessbicarbonate addition to the dialysate, but may not be usable intreatment of all patients.

Known recharging systems do not control the volume of chemical solutionsused in recharging the zirconium phosphate and zirconium oxide, andinstead simply treat the materials with enough recharging chemicals toensure complete recharging. Complete recharging of the sorbent materialsis generally used to cover worst case situations to avoid ammoniabreakthrough in patients with high levels of urea or other ions.Complete recharging of the sorbent materials in each case is wastefuland more costly than recharging the sorbent materials only to the pointnecessary for a future dialysis session. Recharging zirconium phosphateor zirconium oxide in this fashion results in the use of higher volumesof recharging chemicals than may be necessary.

Hence, there is a need for systems and methods that can rechargezirconium phosphate in a zirconium phosphate sorbent module and/orzirconium oxide in a reusable zirconium oxide sorbent module in aprecise and efficient manner. There is a need for systems and methodsthat can more precisely match a recharge process for zirconium phosphateand/or zirconium oxide with actual cartridge need and usage, thuseliminating extra expense, time, money, and chemical usage. There isalso a need for systems and method that can customize the dialysatebicarbonate levels by controlling the zirconium phosphate effluent pH.There is further a need for systems and methods that can control thezirconium phosphate recharging process to create a zirconium phosphatemodule having a desired effluent pH. The need extends to systems andmethods for determining a desired zirconium phosphate effluent pH basedon the needs of the patient and system. There is also a need for systemsand methods that can calculate the amount of recharging solutionsnecessary for recharging the zirconium phosphate and/or zirconium oxide.

SUMMARY OF THE INVENTION

The first aspect of the invention relates to a method. In anyembodiment, the method can include recharging a sorbent material withina sorbent module by pumping one or more recharge solutions through thesorbent module; wherein a volume and/or a concentration of the one ormore recharge solutions is set based on one or more patient parametersand/or one or more dialysis session parameters for a patient and/ordialysis session using the sorbent module.

In any embodiment, the sorbent module can contain zirconium phosphate;the one or more patient parameters can include at least one from a groupconsisting of: pre-dialysis patient potassium, calcium, magnesium,bicarbonate and urea levels, patient weight, patient volume, patientresidual kidney function, patient acidotic state, an average number ofdialysis sessions per week, and an average dialysis session length; andthe one or more dialysis session parameters can include at least onefrom a group consisting of: dialysate flow rate, blood flow rate,dialyzer size, dialyzer type, dialysis time, ultrafiltration rate, apotassium, calcium, magnesium, and bicarbonate dialysis prescription,whether ammonia breakthrough occurred, whether a pH alarm occurred,fluid removed during a session, total volume treated, starting waterquality, URR target, URR achieved, clearance, whether a blood leakoccurred, and whether a hypotensive episode occurred.

In any embodiment, the sorbent module can contain zirconium oxide; theone or more patient parameters can include at least one from a groupconsisting of: patient weight, patient volume, patient residual kidneyfunction, an average number of dialysis sessions per week, and anaverage dialysis session length; and the one or more dialysis sessionparameters can include at least one from a group consisting of:dialysate flow rate, blood flow rate, dialyzer size, dialyzer type,dialysis time, ultrafiltration rate, a potassium, calcium, magnesium,and bicarbonate dialysis prescription, whether ammonia breakthroughoccurred, whether a pH alarm occurred, fluid removed during a session,total volume treated, starting water quality, URR target, URR achieved,clearance, whether a blood leak occurred, and whether a hypotensiveepisode occurred.

In any embodiment, the sorbent module can contain zirconium phosphate,and wherein the one or more patient parameters and/or one or moredialysis session parameters include a total cation and total CO₂ pumpedthrough the sorbent module during a prior dialysis session.

In any embodiment, the total cation and total CO₂ pumped through thesorbent module can be obtained from any one or more of: (a) directmeasurement of total cations and total CO₂ in a dialysate flow pathduring the prior dialysis session; (b) estimation of total cations andtotal CO₂ based on patient weight; (c) estimation of total cations andtotal CO₂ based on a dialysis prescription; (d) estimation of totalcations and total CO₂ based on pre-dialysis patient cation measurementsand/or pre-dialysis patient total CO₂ measurements; (e) estimation oftotal cations and total CO2 based on a number of previous dialysissessions; or (f) combinations thereof.

In any embodiment, the step of recharging the zirconium phosphate cancomprise pumping between 5.0 and 6.0 millimoles of sodium in the one ormore recharge solutions per total milliequivalents of total cationspumped through the sorbent module during the prior dialysis session.

In any embodiment, the step of recharging the zirconium phosphate cancomprise pumping between 0.3 and 1.0 millimoles of acetate in the one ormore recharge solutions per millimole of total CO₂ pumped through thesorbent module during the prior dialysis session.

In any embodiment, the sorbent module can contain zirconium oxide, andthe one or more patient parameters and/or one or more dialysis sessionparameters can include a total phosphate pumped through the sorbentmodule during a prior dialysis session.

In any embodiment, the total phosphate pumped through the sorbent moduleduring the prior dialysis session can be obtained from directmeasurement of phosphate in a dialysate flow path during the priorsession, estimated based on phosphate bleed from zirconium phosphateused in the prior dialysis session and pre-dialysis patient phosphatemeasurements; or estimated based on a total phosphate pumped through thesorbent cartridge in a number of previous dialysis sessions.

In any embodiment, the step of recharging the zirconium oxide cancomprise pumping between 6.0 and 7.5 moles of sodium hydroxide in theone or more recharge solutions per mole of phosphate pumped through thesorbent module during the prior dialysis session.

In any embodiment, the one or more patient parameters and/or one or moredialysis session parameters can include an estimated duration to a nextdialysis session for the patient.

In any embodiment, the sorbent module can contain zirconium phosphate,and the volume of the one or more recharge solutions can be set using anequation V_(r)=v*Q*t*(C_(NH4)+C_(K)+C_(Ca)+C_(Mg)+(a*C_(HCO3)+b));wherein Vr is the volume of the one or more recharge solutions, Q is atime averaged volume flow rate into the sorbent module, t is a sessiontime, C_(NH4), C_(K), C_(Ca), C_(Mg), and C_(HCO3) are averageconcentrations of ammonium ions, potassium ions, calcium ions, magnesiumions and bicarbonate ions entering the sorbent module, a and b arevariables related to a pH of the zirconium phosphate, and v is avariable specific to a recharge process being used.

The features disclosed as being part of the first aspect of theinvention can be in the first aspect of the invention, either alone orin combination, or follow a preferred arrangement of one or more of thedescribed elements.

The second aspect of the invention is drawn to a system. In anyembodiment, the system can comprise a recharging flow path; therecharging flow path comprising one or more recharge solution sources;the one or more recharge solution sources fluidly connectable to aninlet of a sorbent module containing at least one sorbent material; andat least one pump for pumping one or more recharge solutions from theone or more recharge solution sources through the sorbent module; and acontrol system, the control system setting a volume and/or concentrationof the one or more recharge solutions pumped through the sorbent modulenecessary to recharge the sorbent material within the sorbent modulebased on one or more patient parameters and/or one or more dialysissession parameters for a patient and/or dialysis session using thesorbent module.

In any embodiment, the sorbent module can contain zirconium phosphate,and the one or more recharge solution sources can comprise a brinesource, a water source, and a disinfectant source.

In any embodiment, the sorbent module can contain zirconium oxide, andthe one or more recharge solution sources can comprise a base source, awater source, and a disinfectant source.

In any embodiment, the system can comprise a second recharging flowpath; the second recharging flow path comprising one or more rechargesolution sources fluidly connectable to an inlet of a second sorbentmodule containing at least one sorbent material; and at least a secondpump for pumping one or more recharge solutions from the one or morerecharge solution sources through the sorbent module; and the controlsystem can set a volume and/or concentration of the one or more rechargesolutions pumped through the second sorbent module necessary to rechargethe sorbent material within the second sorbent module based on the oneor more patient parameters and/or one or more dialysis sessionparameters for the patient and/or dialysis session using the sorbentmodule.

In any embodiment, the sorbent module can contain zirconium phosphate,the one or more patient parameters can include at least one from a groupconsisting of: pre-dialysis patient potassium, calcium, magnesium,bicarbonate and urea levels, patient weight, patient volume, patientresidual kidney function, an average number of dialysis sessions perweek, patient acidotic state, and an average dialysis session length;and the one or more dialysis session parameters include at least onefrom a group consisting of: dialysate flow rate, blood flow rate,dialyzer size, dialyzer type, dialysis time, ultrafiltration rate, apotassium, calcium, magnesium, and bicarbonate dialysis prescription,whether ammonia breakthrough occurred, whether a pH alarm occurred,fluid removed during a session, total volume treated, starting waterquality, URR target, URR achieved, clearance, whether a blood leakoccurred, and whether a hypotensive episode occurred.

In any embodiment, the sorbent module can contain zirconium oxide; theone or more patient parameters can include at least one from a groupconsisting of: patient weight, patient volume, patient residual kidneyfunction, an average number of dialysis sessions per week, and anaverage dialysis session length; and the one or more dialysis sessionparameters can include at least one from a group consisting of:dialysate flow rate, blood flow rate, dialyzer size, dialyzer type,dialysis time, ultrafiltration rate, a potassium, calcium, magnesium,and bicarbonate dialysis prescription, whether ammonia breakthroughoccurred, whether a pH alarm occurred, fluid removed during a session,total volume treated, starting water quality, URR target, URR achieved,clearance, whether a blood leak occurred, and whether a hypotensiveepisode occurred.

In any embodiment, the sorbent module can contain zirconium phosphate,and the control system can set the volume and/or concentration of theone or more recharge solutions based on a total cation and total CO₂pumped through the sorbent module during a prior dialysis session.

In any embodiment, the sorbent module can contain zirconium oxide, andthe control system can set the volume and/or concentration of the one ormore recharge solutions based on a total phosphate pumped through thesorbent module during a prior dialysis session.

The features disclosed as being part of the second aspect of theinvention can be in the second aspect of the invention, either alone orin combination, or follow a preferred arrangement of one or more of thedescribed elements.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a recharger for recharging a zirconium phosphate moduleand/or a zirconium oxide module.

FIG. 2 shows a graph of the initial zirconium phosphate effluent pH as afunction of the recharge solution pH.

FIG. 3 shows a graph of the zirconium phosphate effluent pH as afunction of an amount of fluid passed through the zirconium phosphatemodule for recharge solutions having various concentrations of acid,base, and salt.

FIG. 4 is a recharging flow path for recharging a zirconium phosphatemodule with two recharge solution sources.

FIG. 5 is a recharging flow path for recharging a zirconium phosphatemodule with a single recharge solution source.

FIG. 6 is a flow chart illustrating the steps in customizing a zirconiumphosphate recharging process.

FIG. 7 is a recharging flow path for recharging a zirconium oxidesorbent module.

DETAILED DESCRIPTION OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used havethe same meaning as commonly understood by one of ordinary skill in theart.

The articles “a” and “an” are used to refer to one or to over one (i.e.,to at least one) of the grammatical object of the article. For example,“an element” means one element or over one element.

The term “acid concentration” refers to the number of moles of an aciddissolved in a given volume of water.

The term “acid solution” refers to an aqueous solution having a pH lessthan 7.

An “acid source” is a fluid or concentrate source from which an acidsolution can be obtained.

The term “ammonia breakthrough” refers to ammonia in a fluid exiting asorbent cartridge.

The term “amount of cations removed by the zirconium phosphate module ina dialysis session” refers to the total number of moles of potassium,calcium, magnesium, ammonium, and other cations adsorbed by zirconiumphosphate in the zirconium phosphate module during dialysis therapy.

The term “average dialysis session length” refers to the amount of timea patient spends undergoing dialysis in a normal dialysis session.

The term “average number of dialysis sessions per week” refer to thenumber of times a patient undergoes dialysis treatment during a normaltreatment schedule.

The term “base concentration” refers to the number of moles of a basedissolved in a given volume of water.

The term “base solution” refers to an aqueous solution having a pH ofgreater than 7.

A “base source” is a fluid or concentrate source from which a basesolution can be obtained.

“Blood flow rate” refers to an amount of blood pumped through anextracorporeal circuit in a given period of time.

The term “blood leak” refers to blood of the patient crossing a dialyzermembrane into a dialysate.

The term “brine source” refers to a source of a solution of salts and/orbuffers containing solutes used in recharging a sorbent material. Incertain embodiments, the brine source can contain a sodium salt, aceticacid, sodium acetate, or combinations thereof.

The term “buffer solution” refers to an aqueous solution containing aweak acid and the conjugate base of the weak acid.

The term “clearance” refers to a rate at which solutes pass through adialyzer membrane.

The term “comprising” includes, but is not limited to, whatever followsthe word “comprising.” Use of the term indicates the listed elements arerequired or mandatory but that other elements are optional and may bepresent.

The term “concentration” refers to an amount of a solute per a givenvolume of a solvent.

The term “consisting of” includes and is limited to whatever follows thephrase “consisting of.” The phrase indicates the limited elements arerequired or mandatory and that no other elements may be present.

The term “consisting essentially of” includes whatever follows the term“consisting essentially of” and additional elements, structures, acts orfeatures that do not affect the basic operation of the apparatus,structure or method described.

The terms “control,” “controlling,” or “controls” refers to the abilityof one component to direct the actions of a second component.

A “control system” can be a combination of components that act togetherto maintain a system to a desired set of performance specifications. Thecontrol system can use processors, memory and computer componentsconfigured to interoperate to maintain the desired performancespecifications. The control system can also include fluid or gas controlcomponents, and solute control components as known within the art tomaintain the performance specifications.

The term “desired initial therapy zirconium phosphate effluent pH”refers to an initial zirconium phosphate effluent pH during therapy setor determined, at least in part, on the needs and capabilities of thesystem and patient.

The terms “determining” and “determine” refer to ascertaining aparticular state or desired state of a system or variable(s).

“Dialysate flow rate” refers to an amount of dialysate pumped through adialysate flow path in a given period of time.

The term “dialysis prescription” refers to dialysis parameters intendedto be used during a dialysis session. In certain embodiments, a“dialysis prescription” can refer to an intended concentration of one ormore solutes in the dialysate used during treatment. For example, acalcium dialysis prescription can refer to the intended calciumconcentration of the dialysate during treatment.

A “dialysis session” is time period that a patient is treated bydialysis, hemodialysis, hemofiltration, ultrafiltration, or other bloodfluid removal therapy.

A “dialysis session parameter” is any data or condition relating to aspecified dialysis session.

The term “dialysis time” refers to the length of time of a specificdialysis session.

The term “dialyzer size” refers to a surface area of a dialyzer membranein a dialyzer.

The term “dialyzer type” refers to whether a specific dialyzer is ahigh-flux or low-flux dialyzer. The type can include othercharacteristics of properties of the dialyzer in addition to flux suchas efficiency and membrane types. Efficiency properties such as membranesize (surface area), porosity, thickness, internal fiber diameters, anddesign (wavelike, straight fiber) are contemplated.

A “disinfectant source” can refer to a fluid source capable ofdestroying or removing biological contaminants.

The term “direct measurement” refers to using a sensor or other systemto determine one or more parameters.

The term “duration to a next dialysis session” refers to an estimatedlength of time between the end of a first dialysis session for a patientand the beginning of a second dialysis session for the same patient.

“Estimated,” to “estimate,” or “estimation” refer to a determination ofone or more parameters indirectly using one or more variables.

The term “fluidly connectable” refers to the ability of providing forthe passage of fluid, gas, or combination thereof, from one point toanother point. The ability of providing such passage can be anyconnection, fastening, or forming between two points to permit the flowof fluid, gas, or combinations thereof. The two points can be within orbetween any one or more of compartments of any type, modules, systems,components, and rechargers.

The term “fluidly connected” refers to a particular state such that thepassage of fluid, gas, or combination thereof, is provided from onepoint to another point. The connection state can also include anunconnected state, such that the two points are disconnected from eachother to discontinue flow. It will be further understood that the two“fluidly connectable” points, as defined above, can from a “fluidlyconnected” state. The two points can be within or between any one ormore of compartments, modules, systems, components, and rechargers, allof any type.

The term “fluid removed during a session” refers to the total amount offluid removed from the blood of a patient during a dialysis session.

A “heater” is a component capable of raising the temperature of asubstance, container, or fluid.

The term “heating” or to “heat” refers to raising the temperature of amaterial.

The term “hypotensive episode” refers to an instance of low bloodpressure in a patient during treatment.

The term “inlet” of a sorbent module can refer to a portion of a sorbentmodule through which fluid, gas, or a combination thereof can be drawninto the sorbent module.

The term “initial therapy zirconium phosphate effluent pH” refers to thepH of a fluid exiting a zirconium phosphate sorbent module at or nearthe beginning of therapy.

The term “mixing” or to “mix” generally refers to causing or more fluidsfrom any source to combine together. For example, “mixing” can includelaminar or turbulent flow at a location in a fluid line or a junction.Another example of “mixing” can include receiving one or more fluids ina component configured to receive fluids from one or multiple sourcesand to mix the fluids together in the component. Additionally, mixingcan refer to the dissolution of a solid or solids with a fluid, whereinthe solid or solids is dissolved in the fluid.

The term “necessary to recharge” a sorbent material refers to an amountof one or more recharge solutions required to result in a sorbentmaterial with a specified functional capacity. In certain embodimentsthe specified functional capacity can be near 100% or can be lowerdepending on the needs of a patient.

The term “number of previous dialysis sessions” can refer to any numberof dialysis sessions for a patient. The number of previous dialysissessions can be 1, 2, 3, or more dialysis sessions.

A “patient” or “subject” is a member of any animal species, preferably amammalian species, optionally a human. The subject can be an apparentlyhealthy individual, an individual suffering from a disease, or anindividual being treated for a disease. In certain embodiments, thepatient can be a human, sheep, goat, dog, cat, mouse or any otheranimal.

The term “patient acidotic state” refers to a pH level in the blood of apatient.

A “patient parameter” is any data that gives relevant information aboutthe health status and therapy requirements of a patient.

“Patient residual kidney function” is a measurement of how well a kidneyof a patient is working as compared to a healthy individual.

“Patient volume” refers to the total amount of water in a patient.

“Patient weight” refers to the mass of a patient.

The term “pH alarm” refers to an indication that the pH of a fluid isoutside of a predetermined range.

The term “pH of the zirconium phosphate” refers to the negative log ofthe concentration of hydrogen ions absorbed onto a given amount ofzirconium phosphate.

“Phosphate bleed” refers to an amount of phosphate ions originallypresent as zirconium phosphate that leak into a fluid pumped through asorbent cartridge.

“Pre-dialysis patient cation measurements” refer to determinations ofcation levels in a patient prior to a dialysis session.

“Pre-dialysis patient total CO₂ measurements” refer to determinations oftotal CO₂ levels in a patient prior to a dialysis session, and caninclude carbon dioxide levels, bicarbonate levels, and carbonate levels.

“Pre-dialysis patient phosphate measurements” refer to a determinationof a phosphate level in a patient prior to a dialysis session.

The term “pre-dialysis patient level,” when referring to specificsolutes or materials, refers to the concentration of the solutes ormaterials in the blood of a patient prior to a dialysis session.

The term “pump” refers to any device that causes the movement of fluidsor gases by applying suction or pressure.

The terms “pumping,” “pumped,” or to “pump” refers to moving a fluid, agas, or a combination thereof with a pump.

A “receiving compartment” is a space within a recharger into which asorbent module to be recharged is placed.

A “recharge solution” is a solution containing appropriate ions forrecharging a specific sorbent material. A recharge solution can be asingle solution containing all necessary ions for recharging a sorbentmaterial. Alternatively, the recharge solution can contain some of theions for recharging the sorbent material, and one or more other rechargesolutions can be used to recharge the sorbent material.

A “recharge solution source” is any fluid or concentrate source fromwhich a recharge solution can be obtained.

“Recharging” refers to treating a sorbent material to restore thefunctional capacity of the sorbent material so as to put the sorbentmaterial back into a condition for reuse or use in a new dialysissession. In some instances, the total mass, weight and/or amount of“rechargeable” sorbent materials remain the same. In some instances, thetotal mass, weight and/or amount of “rechargeable” sorbent materialschange. Without being limited to any one theory of invention, therecharging process may involve exchanging ions bound to the sorbentmaterial with different ions, which in some instances may increase ordecrease the total mass of the system. However, the total amount of thesorbent material will in some instances be unchanged by the rechargingprocess. Upon a sorbent material undergoing “recharging,” the sorbentmaterial can then be said to be “recharged.”

A “recharging flow path” is a path through which fluid can travel whilerecharging sorbent material in a reusable sorbent module.

The term “salt concentration,” as used herein, refers to the number ofmoles of a sodium salt dissolved in a given volume of water.

A “salt solution” refers to an aqueous solution containing dissolvedsodium and counter ions.

A “salt source” is a fluid or concentrate source from which a saltsolution can be obtained.

The term “sequential order” refers to two or more events occurring atdifferent times, as opposed to simultaneously.

The term “session time” refers to a length of time of a dialysissession, from the beginning of dialysis treatment of a patient to theend of the dialysis treatment.

The terms “set based at least in part on” or “set based on” refer to acalculation of a parameter value, wherein the value is a function of atleast one other variable.

A “sorbent cartridge module” or “sorbent module” means a discreetcomponent of a sorbent cartridge. Multiple sorbent cartridge modules canbe fitted together to form a sorbent cartridge of two, three, or moresorbent cartridge modules. In some embodiments, a single sorbentcartridge module can contain all of the necessary materials fordialysis. In such cases, the sorbent cartridge module can be a “sorbentcartridge.” The “sorbent cartridge module” or “sorbent module” cancontain any material for use in sorbent dialysis and may or may notcontain a “sorbent material” or adsorbent. In other words, the “sorbentcartridge module” or “sorbent module” generally refers to the use of the“sorbent cartridge module” or “sorbent module” in sorbent-baseddialysis, e.g., REDY (REcirculating DYalysis), and not that a “sorbentmaterial” is necessarily contained in the “sorbent cartridge module” or“sorbent module.”

The term “sorbent material” refers to a material capable of removingspecific solutes from a fluid. In certain embodiments, the sorbentmaterial can be zirconium oxide or zirconium phosphate.

The phrase “specific to a recharge process being used” can refer to oneor more variables that are used to recharge a sorbent material. Incertain embodiments, the variables can include a composition of arecharge solution, concentrations of one or more solutes in the rechargesolution, temperature of the recharge solution, or flow rate of therecharge solution.

The term “specified temperature” is a temperature range calculated ordetermined prior to recharging a zirconium phosphate module.

The term “starting water quality” can refer to the quality of the waterused in preparing an initial dialysate for a dialysis session. Incertain embodiments, the starting water quality can refer to an amountof solutes dissolved in the water used in preparing the initialdialysate.

A “static mixer” is a component configured to receive fluids from one ormultiple sources and to mix the fluids together. The static mixer mayinclude components that agitate the fluids to further mixing.

The term “temperature sensor” refers to a device for measuring thetemperature of a gas or liquid in a vessel, container, or fluid line.

The term “time averaged volume flow rate” can refer to a volume of fluidmoved per unit time averaged over a dialysis session.

The term “total cation” can refer to an amount of cations in a dialysatethroughout a dialysis session.

“Total CO₂” can refer to the total amount of carbon dioxide, bicarbonateions, and carbonate ions in a dialysate throughout a dialysis session.

The term “total phosphate” refers to the total amount of phosphate ionsin a dialysate throughout a dialysis session.

The term “total volume treated” refers to a total amount of fluid pumpedthrough a sorbent cartridge or sorbent module during dialysis treatment.

The term “ultrafiltration rate” refers to an amount of fluid removedfrom the blood of a patient in a given period of time.

“Urea reduction ratio” or “URR” refers to the amount by which the urealevel of a patient is reduced during treatment. The URR can be expressedas 1 minus the ratio of the patient's ending urea level over thepatient's starting urea level.

“URR achieved” refers to the urea reduction level actually resultingfrom a dialysis session.

“URR target” refers to an intended urea reduction ratio during adialysis session.

A “valve” is a device capable of directing the flow of fluid or gas byopening, closing or obstructing one or more pathways to control whetheror not the fluid or gas to travel in a particular path. One or morevalves that accomplish a desired flow can be configured into a “valveassembly.”

The term “volume” refers to a three-dimensional amount of space occupiedby a material.

A “water source” is a fluid source from which water can be obtained.

“Zirconium oxide” is a sorbent material that removes anions from afluid, exchanging the removed anions for different anions. Zirconiumoxide may also be referred to as hydrous zirconium oxide,

“Zirconium phosphate” is a sorbent material that removes cations from afluid, exchanging the removed cations for different cations

Zirconium Phosphate Recharging

The invention is drawn to systems and methods for recharging and reusingzirconium phosphate and/or zirconium oxide in reusable sorbent modules.FIG. 1 illustrates a recharger for recharging zirconium phosphate orzirconium oxide in a sorbent module. The recharger includes at least afirst receiving compartment 101 for receiving a sorbent module. Thereceiving compartment 101 has a sorbent module inlet and a sorbentmodule outlet (not shown) fluidly connectable to an inlet and outlet ofa sorbent module (not shown). Door 103 controls access to the receivingcompartment 101. A user interface 102 can receive information from auser for controlling the recharge process. The recharger can optionallyinclude a second receiving compartment 104 for receiving a secondsorbent module, containing the same or a different sorbent material forconcurrent recharging of sorbent materials. The recharger can includeany number of receiving compartments for receiving multiple sorbentmodules or various combinations of sorbent modules. The recharger canhave 1, 2, 3, 4, 5, or more receiving compartments for recharging anynumber of sorbent modules. The recharger can be fluidly connectable toone or more recharge solution sources through a recharging flow path.Pumps and valves (not shown) control the movement of fluid from therecharge solution sources through the zirconium phosphate module.

Zirconium phosphate is recharged by pumping one or more solutionscontaining acids, bases, and sodium salts through the zirconiumphosphate module. The hydrogen and sodium ions in the recharge solutionsdisplace potassium, calcium, magnesium, ammonium, and other ions fromeither the dialysate or source water that are bound and adsorbed by thezirconium phosphate during use. The recharged zirconium phosphate withsodium and hydrogen ions can be used during dialysis to remove cationsolutes from the used dialysate. Zirconium oxide can be recharged bypumping one or more solutions containing a hydroxide base through thezirconium oxide sorbent module. The hydroxide ions can displacephosphate ions that are bound and adsorbed by the zirconium oxide duringuse.

The initial therapy zirconium phosphate effluent pH depends on the ratioof hydrogen to sodium ions on the zirconium phosphate. FIG. 2illustrates the effect of the recharge solution pH on the initialtherapy zirconium phosphate effluent pH. The recharge solutions in FIG.2 each contain mixtures of sodium chloride, sodium acetate, and aceticacid. The total sodium concentration in each recharge solution is 4 M,with the ratio of sodium acetate to acetic acid varied to control thepH. As illustrated in FIG. 2, the pH of the recharge solution controlsthe initial therapy zirconium phosphate effluent pH. One of ordinaryskill in the art will understand the initial therapy zirconium phosphateeffluent pH can be controlled by adjusting the pH of the rechargesolution to result in a desired initial therapy zirconium phosphateeffluent pH. The initial therapy zirconium phosphate effluent pH iscontrolled by altering a ratio of hydrogen ions to sodium ions in thezirconium phosphate. A lower pH recharge solution increases the hydrogenion to sodium ion ratio on the recharged zirconium phosphate and lowersthe initial therapy zirconium phosphate pH. A higher pH rechargesolution decreases the hydrogen ion to sodium ion ratio on the rechargedzirconium phosphate and increases the initial therapy zirconiumphosphate effluent pH. The zirconium phosphate effluent pH can becustomized based on the needs of the user by controlling the pH of therecharge solution.

FIG. 3 illustrates the zirconium phosphate effluent pH as a function ofthe volume of dialysate pumped through the zirconium phosphate moduleduring dialysis. As illustrated in FIG. 3, the initial zirconiumphosphate effluent pH is determined by the recharge solutions used. ThepH profile of the zirconium phosphate depends on the mass of thezirconium phosphate and the mass of bicarbonate pumped through thezirconium phosphate module. With a high zirconium phosphate mass, and alow bicarbonate mass pumped through the zirconium phosphate, the initialzirconium phosphate effluent pH may be maintained for an entire therapysession. The zirconium phosphate acts like a buffer and as morebicarbonate is pumped through the zirconium phosphate, the buffercapacity becomes exceeded and the pH will start to increase. Withoutbeing limited to any theory of invention, the final pH plateau may berelated to the composition and pH of the spent dialysate that is pumpedthrough the zirconium phosphate module. However, the initial therapyzirconium phosphate effluent pH is dependent on the pH of the rechargesolution.

Table 1 provides non-limiting examples of recharge solutions and theresulting initial therapy zirconium phosphate effluent pH. In each case,the recharge solution was heated to 80° C. prior to use. As shown inTable 1, a higher ratio of sodium acetate to acetic acid results in ahigher recharge solution pH, and therefore a higher initial therapyzirconium phosphate effluent pH. The relative amounts of acid, base, andsodium salt can be set to generate a recharge solution having thedesired pH.

TABLE 1 Total NaCl NaAce HAce Initial Solution Na (M) (M) (M) (M) pHEffluent PH 1 4.00 4.00 0.00 0.20 2.75 4.40 2 4.00 3.98 0.02 0.20 3.745.42 3 4.00 3.88 0.12 0.40 4.23 5.99 4 4.00 3.60 0.40 0.40 4.75 6.58

Each of the recharge solutions in Table 1 are combinations of sodiumchloride, sodium acetate, and acetic acid. One of skill in the art willunderstand other buffer combinations can be used in place of sodiumacetate and acetic acid, including sodium citrate and citric acid,glycolic acid and sodium glycolate, propionic acid and sodiumpropionate, phosphoric acid and sodium phosphate, or any combinationthereof. The relative amounts of sodium chloride and buffer to achieve adesired initial therapy zirconium phosphate effluent pH will depend onthe pKa of the acid used and can be varied as needed.

The zirconium phosphate module effluent pH affects the amount ofbicarbonate needed during dialysis. Urease in the sorbent cartridgeconverts urea to carbon dioxide and ammonium ions. The carbon dioxideproduced is in equilibrium with bicarbonate in the dialysate. The carbondioxide must be removed from the dialysate by a degasser prior to thedialysate entering the dialyzer. The degasser can be any type ofdegasser known in the art for use in dialysis systems. A high zirconiumphosphate effluent pH during therapy drives the equilibrium towardsbicarbonate formation, resulting in too much bicarbonate in thedialysate for safe treatment. A low zirconium phosphate effluent pHduring therapy drives the equilibrium towards carbon dioxide formation,requiring addition of bicarbonate to the dialysate and placing a highburden on the degasser. One type of degasser suitable for removingcarbon dioxide is a membrane contactor. A membrane contractor is a dualchamber device with a hydrophobic microporous membrane separating thechambers. The hydrophobic microporous membrane allows gas transportwithout allowing water transport across the membrane. Liquid containinggas—in this case CO₂—is passed on one side of the membrane and eitherinert gas or a vacuum is applied to the chamber on the opposite side ofthe membrane. CO₂ is transported from the liquid by diffusion. Anotherexample of a degasser is a vacuum degasser. A vacuum degasser is achamber in which a vacuum can be applied, and which is fluidly connectedto a liquid containing gas to be removed. The liquid is sprayed oratomized in the vacuum chamber. The high surface area of the liquiddroplets allows efficient removal of the gas. One of skill in the artwill understand that any device capable of removing CO₂ from thedialysate can be used. The zirconium phosphate effluent pH can becontrolled by the pH of the recharge solution to meet the needs of thepatient and system. The zirconium phosphate effluent pH is a function ofthe pH, pKa, buffer capacity, sodium chloride level, and temperature ofthe recharge solution. As described, a control system can automaticallydetermine the volumes of each component needed to achieve a desiredinitial therapy zirconium phosphate effluent pH based on each of thefactors.

A zirconium phosphate effluent pH of about 6.5 allows greater than 95%of patients to be treated with a dialysate bicarbonate concentration of25 mM. At a higher pH, fewer patients can be treated. For example, onlyabout 40% of patients can be treated with a zirconium phosphate effluentpH of 6.9 and a dialysate bicarbonate level of 25 mM. At a very low pH,too much acid is added to the dialysate by the zirconium phosphate, andadditional bicarbonate will be necessary to keep the dialysate pH withina safe range, and a degasser is needed to remove carbon dioxide. Theinitial therapy zirconium phosphate effluent pH can be set at any valuecapable of generating safe dialysate, including between 4.0 and 6.9. Adialysate with a lower pH places a higher burden on the degasser.

Any combination of acid, base, and sodium salt capable of generating arecharge solution within the desired pH range can be used in rechargingthe zirconium phosphate. Non-limiting examples of acids and basesinclude sodium acetate and acetic acid, sodium citrate and citric acid,glycolic acid and sodium glycolate, propionic acid and sodiumpropionate, phosphoric acid and sodium phosphate, or any combinationthereof. One of skill in the art will understand the relative amounts ofacid and base needed to generate a recharge solution with a desired pHwill vary with the pKa of the acid. The relative volumes of the acid andbase can be varied based on the pKa of the particular acid and baseused. For example, a recharge solution with 3.1 M sodium chloride, 0.9 Msodium acetate, and 0.6 M acetic acid has a pH of 4.6, which willgenerate a zirconium phosphate effluent pH of 6.5.

As described, the zirconium phosphate effluent pH during therapycontrols the equilibrium between carbon dioxide and bicarbonate in thedialysate. Carbon dioxide and bicarbonate in the dialysate generallycomes from two sources, the conversion of urea to carbon dioxide and anybicarbonate added to the dialysate. To minimize the amount of additionalbicarbonate required, the zirconium phosphate effluent pH can be set toa higher value, at least for patients that can be effectively treatedwith a higher dialysate bicarbonate level. The higher zirconiumphosphate effluent pH during therapy drives the bicarbonate/carbondioxide equilibrium towards bicarbonate formation, retaining bicarbonategenerated from the urea removed from the patient.

A control system in the recharger can determine the optimal initialtherapy zirconium phosphate effluent pH for a patient based on thepatient's pre-treatment bicarbonate and urea levels. For alkaloticpatients, a lower initial therapy zirconium phosphate effluent pH can beselected to minimize the amount of bicarbonate formed from the patient'surea. For other patients, a higher initial therapy zirconium phosphateeffluent pH can be selected to generate a higher amount of bicarbonatefrom the patient's urea, reducing the additional bicarbonate needed andminimizing the burden on the degasser. Alternatively, a user interfacecan be provided, with the user directly inputting the desired initialtherapy zirconium phosphate effluent pH.

The control system can be any component capable of monitoring andaffecting the states of the recharger. The control system can useprocessors, memory and computer components to carry out the functionsdescribed. The control system is in communication with the pumps andvalves of the recharging flow paths and can control the pumps and valvesin accordance with stored instructions. The control system is also incommunication with various sensors in the recharging flow paths. Thecontrol system receives data from the sensors and controls the pumps andvalves of the recharging flow path on the basis of the data inaccordance with stored instructions. Factors affecting the desiredinitial therapy zirconium phosphate effluent pH, such as patientpre-treatment urea and bicarbonate levels can be communicated to thecontrol system by any means known in the art. The control system canautomatically determine the optimal recharging solution pH usingmathematical algorithms or look-up tables and operate the pumps andvalves of the recharging flow paths to control the recharging process.

FIG. 4 illustrates a non-limiting embodiment of a recharging flow path401 for customization of a recharging solution. A zirconium phosphatemodule 402 can connect to the recharging flow path 401 through zirconiumphosphate inlet 403 and zirconium phosphate outlet 404. Pump 407provides a driving force for moving fluids through the recharging flowpath 401. A salt or brine source 405, containing a salt solution such assodium chloride or mixtures of sodium chloride and sodium acetate, andan acid source 406 containing an acid solution, such as acetic acid, arefluidly connected to the recharging flow path 401. Valve 408 determinesthe amount of each recharge solution that enters the recharging flowpath 401 to generate a recharge solution having a specified acidconcentration, base concentration, and salt concentration, and can becontrolled by the control system. Sodium chloride and/or sodium acetatefrom brine source 405 is pumped through the recharging flow path 401 tothe zirconium phosphate module 402. Acid from acid source 406 can bepumped into the recharging flow path 401 at a ratio to the sodiumchloride and sodium acetate based on the desired recharge solution pH.For example, acetic acid from acid source 406 can be metered in to thesodium chloride and/or sodium acetate in recharging flow path 401 at aspecified rate to control the pH of the resulting recharge solution. Ahigher sodium chloride to acid ratio will result in a recharge solutionat a higher pH, while a lower sodium chloride to acid ratio will resultin a recharge solution at a lower pH. The control system canautomatically control valve 408 to control the ratio of sodium chlorideto acid. Alternatively, the acid source 406 can contain a buffersolution, such as sodium acetate and acetic acid, and the control systemcan control the ratio of sodium chloride and buffer to control therecharge solution pH. A static mixer 409 can be included to ensurecomplete mixing of the acid and sodium solutions. Alternatively, theacid and sodium solutions can be mixed through the mixing of the twofluid streams in the recharging flow path 401. One of skill in the artwill understand that different pump and valve arrangements can be usedwith the system illustrated in FIG. 4. For example, the brine source 405and acid source 406 can be connected to the recharging flow path 401through separate pumps, allowing simultaneous addition of sodiumchloride and acid to the recharging flow path 401.

Alternatively, a system as illustrated in FIG. 4 can have sodiumchloride and an acid in a first recharge solution source, with a basesolution, such as sodium hydroxide, in a base source. The sodiumchloride and acid can be pumped through the zirconium phosphate module,with the base solution metered in to generate a recharge solution withthe desired pH in situ.

The recharging flow path 401 in FIG. 4 can also recharge the zirconiumphosphate module 402 by addition of recharging solutions in a sequentialorder. The acid solution from acid source 406 can be pumped through thezirconium phosphate module 402 first, followed by sodium chloride andsodium acetate from brine source 405. The initial acid solution willgenerate a zirconium phosphate module 402 at a low pH, and the lateraddition of sodium chloride and sodium acetate will raise the pH assodium ions displace the hydrogen ions initially adsorbed by thezirconium phosphate. The resulting zirconium phosphate effluent pH willdepend on the amount of sodium chloride and sodium acetate pumpedthrough the zirconium phosphate module 402 in the second step. Thecontrol system can control the sodium chloride and sodium acetateaddition to generate a zirconium phosphate module 402 with the desiredinitial therapy zirconium phosphate effluent pH. A pH sensor (not shown)can be placed in the zirconium phosphate effluent to determine thezirconium phosphate effluent pH, and the sodium chloride can be stoppedwhen the pH sensor reads the desired pH. The concentration and amount ofsodium chloride and sodium acetate pumped through the zirconiumphosphate module 402 will control the initial therapy zirconiumphosphate effluent pH after recharging. Alternatively, the sodiumchloride and sodium acetate can be pumped through the zirconiumphosphate module 402 first, followed by the acid.

FIG. 5 illustrates a recharging flow path 501 with a single rechargesolution source 505 containing a sodium salt and buffer. A zirconiumphosphate module 502 can be fluidly connected to the recharging flowpath 501 through zirconium phosphate inlet 503 and zirconium phosphateoutlet 504. Pump 506 provides a driving force for moving fluids throughthe recharging flow path 501. Recharge solution source 505 is fluidlyconnected to the recharging flow path 501. A recharge solution inrecharge solution source 505 at the desired recharge solution pH can bepumped through the zirconium phosphate module 502 to recharge thezirconium phosphate. To alter the initial therapy zirconium phosphateeffluent pH, the pH of the recharge solution can be altered. The usercan add solid or concentrated sources of an acid, a base, a salt, orcombinations thereof, to control the pH of the recharge solution togenerate a recharge solution having a specified acid concentration, baseconcentration, and salt concentration. The control system can inform theuser of the correct amounts of acid, base, or salt to add to therecharge solution source 505. Alternatively, a separate source of acid,base, or salt can be included in the recharger, and the system canautomatically add the correct amount to the recharge solution source 505based to generate a recharge solution with the desired pH. For example,a recharge solution with a pH of 4.6 can be placed in the rechargesolution source 505 and used for the majority of patients. For severelyalkalotic patients, the system or user can add a predetermined amount ofacid to lower the recharge solution pH. To reduce the amount ofbicarbonate needed during therapy, the system or user can add apredetermined amount of base to raise the recharge solution pH.

FIG. 7 illustrates a non-limiting embodiment of a recharging flow path701 for recharging zirconium oxide in a reusable zirconium oxide sorbentmodule 702. The zirconium oxide sorbent module 702 can be fluidlyconnected to the recharging flow path 701 through zirconium oxide moduleinlet 703 and zirconium phosphate module outlet 704. Pump 706 provides adriving force for moving fluids through the recharging flow path 701.Recharge solution source 705 is fluidly connected to the recharging flowpath 701 and can be a base source. The recharge solution source 705 cancontain sodium hydroxide at a specified concentration. A control system(not shown) can set the volume of sodium hydroxide pumped through thezirconium oxide sorbent module 702 based on one or more patientparameters and/or one or more dialysis session parameters.

One of skill in the art will understand the recharging flow pathsillustrated in FIGS. 4-5 and 7 can include additional fluid sources. Awater source can provide water for flushing and rinsing of the zirconiumphosphate module and/or zirconium oxide module before and afterrecharging. A water source can also provide in-line dilution of any ofthe recharge solutions, allowing a more concentrated recharge solutionin the recharge solution sources. A disinfectant source can provide adisinfection solution for disinfecting the zirconium phosphate and/orzirconium oxide module prior to recharging. The disinfection solutioncan be any solution capable of disinfecting the zirconium phosphateand/or zirconium oxide sorbent module, including a peracetic acidsolution, a citric acid solution, or any other disinfectant.

The recharger can include multiple recharging flow paths for rechargingmultiple sorbent modules. For instance, a single recharger can includetwo or more recharging flow paths for recharging two or more zirconiumphosphate sorbent modules or two or more zirconium oxide sorbentmodules. Additionally, a single recharger can include both a zirconiumphosphate recharging flow path and a zirconium oxide recharging flowpath for recharging both a zirconium phosphate sorbent module and azirconium oxide sorbent module. One or more recharge solution sourcescan be shared by both recharging flow paths, or separate rechargesolution sources can be used in each flow path.

The total volume of recharge solution needed to recharge the zirconiumphosphate depends on the amount of cations removed by the zirconiumphosphate in the previous dialysis session and the amount of total CO₂fed through the zirconium phosphate during the previous dialysissession, which in turn depend on a number of patient and/or dialysisparameters. Patient parameters affecting the amount of cations removedby the zirconium phosphate and the amount of CO₂ fed through thezirconium phosphate include pre-dialysis patient potassium, calcium,magnesium, bicarbonate and urea levels; patient weight, patient volume,patient residual kidney function, an average number of dialysis sessionsper week, patient acidotic state, and an average dialysis sessionlength. Dialysis parameters affecting the amount of cations removed fromthe zirconium phosphate include dialysate flow rate, blood flow rate,dialyzer size, dialyzer type, dialysis time, ultrafiltration rate, apotassium, calcium, magnesium, and bicarbonate dialysis prescription,whether ammonia breakthrough occurred, whether a pH alarm occurred,fluid removed during a session, total volume treated, starting waterquality, URR target, URR achieved, clearance, whether a blood leakoccurred, and whether a hypotensive episode occurred.

The total volume of recharge solution needed to recharge the zirconiumoxide depends on the amount of phosphate removed by the zirconium oxidein the previous dialysis session, which in turn can depend on a numberof patient and/or dialysis parameters. Patient parameters affecting theamount of phosphate removed by the zirconium oxide include patientweight, patient volume, patient residual kidney function, an averagenumber of dialysis sessions per week, and an average dialysis sessionlength. Dialysis parameters affecting the amount of phosphate removed bythe zirconium oxide include dialysate flow rate, blood flow rate,dialyzer size, dialyzer type, dialysis time, ultrafiltration rate, apotassium, calcium, magnesium, and bicarbonate dialysis prescription,whether ammonia breakthrough occurred, whether a pH alarm occurred,fluid removed during session, total volume treated, starting waterquality, URR target, URR achieved, clearance, whether a blood leakoccurred, and whether a hypotensive episode occurred.

Usage of a zirconium phosphate module and/or a zirconium oxide module bya patient can be tracked with an RFID tag, barcode, or other trackingdevice. The control system can receive any one or more of the patientparameters influencing the amount of recharge solution needed anddetermine the necessary volume of the recharge solution for rechargingthe zirconium phosphate module and/or zirconium oxide module. In certainembodiments, the control system can receive patient and dialysisparameters from the prior usage and history of the sorbent cartridge andpatient to determine the necessary volume of the recharge solution forrecharging the zirconium phosphate module and/or zirconium oxide module.The control system can use all prior history and usage of the patientand sorbent modules, or can use the prior history and usage over anyspecified length of time. In certain embodiments, the control system canuse the patient and dialysis parameters from a previous week, month,year, or longer period of time.

A tracking component, such as an RFID tag or bar code, can be affixed tothe sorbent modules, and automatically read by the control system atvarious times, including prior to dialysis, after dialysis, prior torecharging, and after recharging. A single reader can read and track thesorbent modules at each stage of use, or separate readers can beincluded with the rechargers and dialysis systems to track usage of thesorbent modules. The tracking system can track which patients used thesorbent modules and the dialysis parameters that affect the amount ofrecharge solutions necessary to recharge the sorbent modules. Theparameters can be communicated to the control system, which can thendetermine the amount of recharge solution necessary through mathematicalalgorithms, look-up tables or a combination thereof.

Generally, about 5.5 millimoles of sodium in the recharge solution isrequired per total milliequivalents of cations(ammonium+potassium+calcium+magnesium) that are fed through thezirconium phosphate during therapy in order to recover greater than 90%of the original capacity of the zirconium phosphate. Lower moles ofsodium are needed per mole of cations loaded on the zirconium phosphatefor full recharging at elevated temperatures, and less recharge solutionis needed with a higher recharge solution concentration. A higher amountof sodium may be needed if the recharging is conducted at roomtemperature. The recharge solution can have any amount of sodium ionsrelative to the amount of cations loaded on the zirconium phosphate,including sodium ions between 5 and 15 times greater than the amount ofcations loaded on the zirconium phosphate. In certain embodiments, thetotal millimoles of sodium pumped through the zirconium phosphate moduleduring recharging can be between 5.0 and 15.0 millimoles of sodium permilliequivalent of cations, between 5.0 and 10.0 millimoles of sodiumper milliequivalent of cations, between 5.0 and 6.0 millimoles of sodiumper milliequivalent of cations, between 7.0 and 12.0 millimoles ofsodium per milliequivalent of cations, between 10.0 and 12.5 millimolesof sodium per milliequivalent of cations, or between 10.0 and 15.0millimoles of sodium per milliequivalent of cations.

Generally, about 0.6-millimoles of total acetate (sodium acetate+aceticacid) in the recharge solution is required per millimole of total CO₂(CO₂+HCO₃ ⁻+CO₃ ²⁻) that is fed through the zirconium phosphate duringtherapy in order to achieve the desired effluent pH profile during thenext dialysis session. In certain embodiments, the total millimoles ofacetate pumped through the zirconium phosphate module during rechargingcan be between 0.3 and 1.0 millimoles of acetate per millimole of totalCO₂, between 0.3 and 0.5 millimoles of acetate per millimole of totalCO₂, between 0.5 and 0.7 millimoles of acetate per millimole of totalCO₂, or between 0.6 and 1.0 millimoles of acetate per millimole of totalCO₂.

As described, the patient acidotic state can be used to determine adesired zirconium phosphate effluent pH for a future therapy session.For alkalotic patients, a lower initial therapy zirconium phosphateeffluent pH can be selected to minimize the amount of bicarbonate formedfrom the patient's urea. The initial therapy zirconium phosphateeffluent pH depends on the concentrations and volume of rechargesolutions used, and can be used by the control system in determining avolume and/or concentration of the recharge solutions.

The amount of recharge solution needed can also depend on thetemperature of the recharge solution. The recharging flow pathsdescribed can include a heater and optionally a heat exchanger forheating the recharge solution to a specified temperature prior topumping the recharge solution through the zirconium phosphate module, asrecharging zirconium phosphate may be more efficient at elevatedtemperatures. A temperature sensor determines the temperature of therecharge solution, and the control system can take temperature intoaccount in determining the total amount of recharge solution necessary.The recharge solution can be heated to any specified temperature,including between 60-90° C., 60-70° C., 60-80° C., 75-85° C., or 80-90°C. During recharging, the control system can use only the volume ofrecharge solution necessary based on the total amount of cations loadedonto the zirconium phosphate, the concentration of the rechargesolution, and the temperature of the recharge solution, saving on costsand materials.

Generally, about 6.7 moles of sodium hydroxide is required to rechargethe zirconium oxide per mole of phosphate fed through the zirconiumoxide module during a previous dialysis session. In certain embodiments,the total moles of sodium hydroxide pumped through the zirconium oxidemodule during recharging can be between 5.0 and 8.4 moles of sodiumhydroxide per mole of phosphate, between 5.0 and 6.5 moles of sodiumhydroxide per mole of phosphate, between 6.0 and 7.0 moles of sodiumhydroxide per mole of phosphate, between 6.0 and 8.0 moles of sodiumhydroxide per mole of phosphate, or between 6.5 and 8.4 moles of sodiumhydroxide per mole of phosphate.

The total cations and total CO₂ pumped through the zirconium phosphateduring a dialysis session can be obtained by direct measurement with oneor more sensors in a dialysate flow path during treatment, or estimated.The estimates of total cations and total CO₂ can be based on patientweight, the dialysate prescription, pre-dialysis patient cationmeasurements and/or pre-dialysis patient total CO₂ measurements, or anycombination thereof. Similarly, the total phosphate pumped through thezirconium oxide during a dialysis session can be obtained by directmeasurement by a sensor in the dialysate flow path or estimated based onphosphate bleed from the zirconium phosphate and pre-dialysis patientphosphate measurements. In certain embodiments, the total cations, totalCO₂, and total phosphate pumped through the sorbent materials can beestimated based on a number of previous dialysis sessions. The values orparameters used can be tracked for a patient over any number of previousdialysis sessions and used to estimate the total cations and total CO₂pumped through the zirconium phosphate in the immediately prior dialysissession. The number of previous dialysis sessions used can be any numbern of previous dialysis sessions, where n is 1 or greater. In certainembodiments, the number of previous dialysis sessions can be between1-5, 2-10, 5-10, or greater number of dialysis sessions. The number ofprevious dialysis sessions can also be set as a length of time,including dialysis sessions over the prior week, month, year, or anyother length of time.

In a non-limiting embodiment, the total urea removed by the zirconiumphosphate can be given by EQ(1).Total urea=Q _(d) *t*C _(Durea)  EQ(1)Where Q_(d) is the dialysate flow rate, t is the length of the previousdialysis session, and C _(Durea) is the average urea concentration inthe dialysate. As described, the average urea concentration of thedialysate can be measured directly by a sensor in the dialysate flowpath, or can be estimated. EQ(2) provides an alternative method fordetermining the amount of urea removed by the zirconium phosphate.Total urea=V _(prp) *C _(Burea,prp) −V _(post) *C _(Burea,post)  EQ(2)Where V_(prp) is a patient water volume prior to the dialysis session,V_(post) is the patient water volume after the dialysis session,C_(Burea, prp) is the patient blood urea level prior to the dialysissession, and C_(Burea, post) is the patient blood urea level after thedialysis session. The patient water volume before the dialysis sessioncan be measured via bioimpedance, or estimated based on the patientweight. After the dialysis session, the patient water volume can bemeasured by bioimepedance, estimated based on weight, or determined bythe pre-session patient water volume minus the total ultrafiltrationduring the dialysis session. The patient blood urea level prior to thedialysis session can be measured directly in the patient's blood, or canbe estimated based on populations averages and then adjusted for aspecific patient. The patient blood urea level prior to the dialysissession can also be estimated based on therapy frequency or the day ofthe week. The post-dialysis session blood urea level can be measureddirectly, or estimated based on the pre-dialysis blood urea level andthe urea reduction ratio (URR), where URR is given by EQ(3).

$\begin{matrix}{{URR} = {{1 - {\frac{{CBurea},{post}}{{CBurea},{prp}}\mspace{14mu}{or}\mspace{14mu} C_{{Burea},{post}}}} = {{URR}*C_{{Burea},{prp}}}}} & {{EQ}\mspace{14mu}(3)}\end{matrix}$The URR can be estimated based on the patient volume, the dialyzerclearance, and the length of the session, as provided by EQ(4).URR=1−e ^(−kt/V)  EQ(4)Where k is the dialyzer clearance, t is the session time, and v is thepatient volume. The dialyzer clearance can be determined using EQ(5).

$\begin{matrix}{{k = \frac{e^{s} - 1}{\frac{e^{s}}{Q_{B}} - \frac{1}{Q_{d}}}};{S = \frac{K_{o}{A\left( {1 - \frac{Q_{B}}{Q_{D}}} \right)}}{Q_{B}}}} & {{EQ}\mspace{14mu}(5)}\end{matrix}$Where Q_(B) is the blood flow rate during the dialysis session, Q_(D) isthe dialysate flow rate during the dialysis session, and K_(o)A is thedialyzer mass transfer coefficient, which can be obtained from thedialyzer spec sheet.

EQ(6) provides a non-limiting equation for determining the total calciumremoved by the zirconium phosphate.Total calcium=Q _(d) *t*C _(D) ,ca  EQ(6)Where Q_(d) is the dialysate flow rate, t is the length of the previousdialysis session, and C _(D, Ca) is the average calcium concentration inthe dialysate entering the sorbent cartridge. The average calciumconcentration of the dialysate can be measured directly by a sensor inthe dialysate flow path, or can be estimated to be the dialysateprescription level. The total magnesium removed by the zirconiumphosphate can be determined in the same manner as the total calcium. Thetotal potassium removed by the zirconium phosphate can be determined inthe same way as the total calcium, plus additional potassium from thepatient, which can be estimated based on patient blood measurements orassumed using the pre-therapy potassium blood levels.

EQ (7) provides a non-limiting example of an equation for calculating anecessary amount of recharge solution for recharging zirconiumphosphate.V _(r) =v*Q*t*(C _(NH4) +C _(K) +C _(Ca) +C _(Mg)+(a*C _(HCO3)+b))  EQ(7)Where Vr is the volume of recharge solution necessary to recharge thezirconium phosphate, Q is the time averaged volume flow rate into thezirconium phosphate sorbent module, t is the session time, C_(NH4),C_(K), C_(Ca), C_(Mg), and C_(HCO3) are average concentrations ofammonium ions, potassium ions, calcium ions, magnesium ions andbicarbonate ions entering the zirconium phosphate sorbent module, a andb are variables related to the pH of the zirconium phosphate and relateto an amount of hydrogen released from the zirconium phosphate, and v isa variable specific to the recharge process being used. In the case ofrecharging with a recharge solution having 4.7 M NaCl, 0.4 M sodiumacetate, and 0.4 M acetic acid at 80° C., v=1.10, a=0.14 and b=9.21. Oneof skill in the art will understand that the values of a, b, and v canbe readily derived based on the pH of the zirconium phosphate and thespecific conditions being used for recharging.

The values for the concentrations used in EQ(7) can be determined frombasic transport models across the dialyzer and mass balance equations,such as those shown in EQ's(1-6), on the dialysate circuit used and arereadily derived by those skilled in the art. The transport model acrossthe dialyzer can include the dialysate flow rate, blood flow rate,dialyzer size and koA, pre-dialysis patient levels of the solutes,concentrations in the dialysate for the solutes, patient weight andvolume, and ultrafiltration rate. The mass balance on the dialysatecircuit can include the concentration of the solutes in the spentdialysate (determined from the dialyzer transport model), the volume ofsource water used, and the starting water quality, which includes theconcentrations of the solutes in the starting water used to generate theinitial dialysate. The pre-dialysis patient levels of the solutes or thepatient acidotic state can be measured with a blood analyzer before thetreatment or can be estimated based on the patient's dialysis scheduleand typical session parameters like frequency per week, session time,patient weight, patient acidotic state, and time since last session. Themethods to estimate the concentration from these values can be derivedby one skilled in the art.

As described, specific alarms or instances during treatment can alsoaffect the concentration and volume of the recharge solution necessaryfor recharging the sorbent modules. Ammonia breakthrough could indicatethat the zirconium phosphate was fully loaded with cations, and therecharge volume may be increased accordingly. For example, if ammoniabreakthrough occurs, 7.0 L of a recharge solution having 4.7 M NaCl, 0.4M sodium acetate, and 0.4 M acetic acid can be used to recharge thezirconium phosphate. Alternatively, the total concentrations of sodiumand acetate in the recharge solution can be increased and the volume ofrecharge solution kept the same. In certain embodiments, the volumeand/or concentration of the recharge solution can be increased beyondthat required for recharging the sorbent material to ensure completerecharging.

A pH alarm could indicate that the zirconium phosphate was fullytitrated with bicarbonate during treatment, and the recharge solutionvolume or concentration should be increased accordingly. For example,7.0 L of a recharge solution having 4.7 M NaCl, 0.4 M sodium acetate,and 0.4 M acetic acid can be used to recharge the zirconium phosphate inthe event of a pH alarm, or the concentrations of acetate in therecharge solution increased.

A blood leak could result in a need to increase the volume of disinfectsolution needed to fully disinfect the zirconium phosphate or zirconiumoxide or to compensate for less efficient recharge due to more proteinexposure of the zirconium phosphate. In certain embodiments, 0.1 L extraof disinfectant solution can be used for each instance of a blood leakduring treatment, depending on the disinfectant used and theconcentration.

In certain embodiments, an estimated duration to a next dialysis sessionfor the patient can be used in setting the recharge solution volumeand/or concentration. If the duration to the next dialysis session willbe longer, the patient may have a higher urea level and a higherphosphate level at the start of the next dialysis session, and a highercapacity required for the zirconium phosphate and zirconium oxide. Insuch instances, the volume and/or concentration of the rechargesolutions can be increased to compensate for the expected higherrequirements in the next dialysis session.

Given that about 6.7 moles of sodium hydroxide is required to rechargethe zirconium oxide per mole of phosphate fed through the zirconiumoxide module during a previous dialysis session, a person of ordinaryskill can calculate the total volume of sodium hydroxide necessary forrecharging. For example, if 10 moles of phosphate are fed through thezirconium oxide module during a previous dialysis session, about 67moles of sodium hydroxide will be required for recharging.

FIG. 6 is a flow chart illustrating the steps in customizing a zirconiumphosphate recharging process based. In step 601, a desired initialtherapy zirconium phosphate effluent pH can be determined. As described,the desired initial therapy zirconium phosphate effluent pH can be basedon one or more patient parameters and system parameters, including thepatient's pre-treatment bicarbonate and urea levels, as well as theavailable of additional bicarbonate to be added during dialysis and thedegassing capabilities of the system. The desired initial therapyzirconium phosphate effluent pH can be determined by the control systembased on the patient parameters and/or system parameters, or directlyentered by a user through a user interface. In step 602 theconcentrations of acid, base, and sodium salt in the recharge solutioncan be determined. The described concentrations depend on the pKa of theacid or buffer, the buffer capacity, and the temperature of the rechargesolution, and can be automatically determined by the control system.Where a single recharge solution source is used, the control system canautomatically inform the user to add a specific amount of acid, base, orsalt to the recharge solution. Where two or more recharge solutionsources are used, the control system can determine the relative amountsof fluid needed from each recharge solution source.

In step 604, the system can determine an amount of cations removed bythe zirconium phosphate module in a previous dialysis session. Theamount of cations removed by the zirconium phosphate module depends onthe pre-dialysis patient potassium, calcium, magnesium, and urea levelsof the patient, as well as patient weight, patient bicarbonate level,dialysate flow rate, blood flow rate, dialyzer size, dialysis time,ultrafiltration rate, and the potassium, calcium, magnesium, andbicarbonate dialysis prescription. The described patient parameters canautomatically be received by the control system through a trackingdevice on the zirconium phosphate module tracking usage. Alternatively,the described patient parameters can be input directly by the user basedon the patient's medical records or other information. The describedpatient parameters can also be assumed by the system based on patientnorms and settings entered into the system based on patient blood labs.

In step 603, the amount of acid, base, and sodium salt necessary toachieve the desired initial therapy zirconium phosphate effluent pH canbe determined. Using the total volume determined in step 604, and theconcentrations determined in step 602, the control system canautomatically determine the pump rates and/or valve switching necessaryto recharge the zirconium phosphate from one or more recharge solutionsources and control the pumps and valves to generate the rechargesolution. In step 605, the control system controls the pumps and valvesto recharge the zirconium phosphate module.

One of skill in the art will understand that one or more of the stepsillustrated in FIG. 6 can be eliminated. For example, if a desiredinitial therapy zirconium phosphate effluent pH of 6.5 will be used fornearly all patients, the system can skip steps 601 and 602. Theconcentrations of the acid, base, and salt necessary to generate arecharge solution with the correct pH can be stored in a system memoryand used each time. If a specified recharge solution volume is used eachtime, step 604 can also be eliminated.

One skilled in the art will understand that various combinations and/ormodifications and variations can be made in the described systems andmethods depending upon the specific needs for operation. Moreover,features illustrated or described as being part of an aspect of theinvention may be used in the aspect of the invention, either alone or incombination, or follow a preferred arrangement of one or more of thedescribed elements.

We claim:
 1. A method, comprising the steps of: recharging a sorbentmaterial within a sorbent module (402, 702) by pumping one or morerecharge solutions through the sorbent module; wherein a volume and/or aconcentration of the one or more recharge solutions is set based on oneor more patient parameters and/or one or more dialysis sessionparameters for a patient and/or dialysis session using the sorbentmodule.
 2. The method of claim 1, wherein the sorbent module containszirconium oxide, and wherein the one or more patient parameters and/orone or more dialysis session parameters include a total phosphate pumpedthrough the sorbent module during a prior dialysis session.
 3. Themethod of claim 2, wherein the total cation and total CO₂ pumped throughthe sorbent module is obtained from any of: a. direct measurement oftotal cations and total CO₂ in a dialysate flow path during the priordialysis session; b. estimation of total cations and total CO₂ based onpatient weight; c. estimation of total cations and total CO₂ based on adialysis prescription; d. estimation of total cations and total CO₂based on pre-dialysis patient cation measurements and/or pre-dialysispatient total CO₂ measurements; e. estimation of total cations and totalCO2 based on a number of previous dialysis sessions; or f. combinationsthereof.
 4. The method of claim 2, wherein the step of recharging thezirconium phosphate comprises pumping: (a) between 5.0 and 6.0millimoles of sodium in the one or more recharge solutions per totalmilliequivalents of total cations pumped through the sorbent moduleduring the prior dialysis session; or (b) between 0.3 and 1.0 millimolesof acetate in the one or more recharge solutions per millimole of totalCO₂ pumped through the sorbent module during the prior dialysis session.5. The method of claim 2, wherein the total phosphate pumped through thesorbent module during the prior dialysis session is obtained from directmeasurement of phosphate in a dialysate flow path during the priorsession, estimated based on phosphate bleed from zirconium phosphateused in the prior dialysis session and pre-dialysis patient phosphatemeasurements, or estimated based on a total phosphate pumped through thesorbent cartridge in a number of previous dialysis sessions.
 6. Themethod of claim 2, wherein the step of recharging the zirconium oxidecomprises pumping between 6.0 and 7.5 moles of sodium hydroxide in theone or more recharge solutions per mole of phosphate pumped through thesorbent module during the prior dialysis session.
 7. The method of claim1, wherein the one or more patient parameters and/or one or moredialysis session parameters include an estimated duration to a nextdialysis session for the patient.
 8. The method of claim 1, wherein thesorbent module contains zirconium phosphate, and wherein the volume ofthe one or more recharge solutions is set using an equationV_(r)=v*Q*t*(C_(NH4)+C_(K)+C_(Ca)+C_(Mg)+(a*C_(HCO3)+b)); wherein Vr isthe volume of the one or more recharge solutions, Q is a time averagedvolume flow rate into the sorbent module, t is a session time, C_(NH4),C_(K), C_(Ca), C_(Mg), and C_(HCO3) are average concentrations ofammonium ions, potassium ions, calcium ions, magnesium ions andbicarbonate ions entering the sorbent module, a and b are variablesrelated to a pH of the zirconium phosphate, and v is a variable specificto a recharge process being used.
 9. A system comprising: a rechargingflow path (401, 701); the recharging flow path comprising one or morerecharge solution sources; the one or more recharge solution sources(405, 406, 705) fluidly connectable to an inlet (403, 703) of a sorbentmodule (402, 702) containing at least one sorbent material; and at leastone pump (407, 706) for pumping one or more recharge solutions from theone or more recharge solution sources through the sorbent module; and acontrol system, the control system setting a volume and/or concentrationof the one or more recharge solutions pumped through the sorbent modulenecessary to recharge the sorbent material within the sorbent modulebased on one or more patient parameters and/or one or more dialysissession parameters for a patient and/or dialysis session using thesorbent module.
 10. The system of claim 9, wherein: the sorbent module(401) contains zirconium phosphate, and wherein the one or more rechargesolution sources comprise a brine source (405), a water source, and adisinfectant source; or wherein the sorbent module contains zirconiumoxide (702), and wherein the one or more recharge solution sourcescomprise a base source (705), a water source, and a disinfectant source.11. The system of claim 9, further comprising a second recharging flowpath; the second recharging flow path comprising one or more rechargesolution sources fluidly connectable to an inlet of a second sorbentmodule containing at least one sorbent material; and at least a secondpump for pumping one or more recharge solutions from the one or morerecharge solution sources through the sorbent module; wherein thecontrol system sets a volume and/or concentration of the one or morerecharge solutions pumped through the second sorbent module necessary torecharge the sorbent material within the second sorbent module based onthe one or more patient parameters and/or one or more dialysis sessionparameters for the patient and/or dialysis session using the sorbentmodule.
 12. The system of claim 9, wherein the sorbent module containszirconium phosphate, wherein the one or more patient parameters includeat least one from a group consisting of: pre-dialysis patient potassium,calcium, magnesium, bicarbonate and urea levels, patient weight, patientvolume, patient residual kidney function, patient acidotic state, anaverage number of dialysis sessions per week, and an average dialysissession length; and wherein the one or more dialysis session parametersinclude at least one from a group consisting of: dialysate flow rate,blood flow rate, dialyzer size, dialyzer type, dialysis time,ultrafiltration rate, a potassium, calcium, magnesium, and bicarbonatedialysis prescription, whether ammonia breakthrough occurred, whether apH alarm occurred, fluid removed during a session, total volume treated,starting water quality, URR target, URR achieved, clearance, whether ablood leak occurred, and whether a hypotensive episode occurred.
 13. Thesystem of claim 9, wherein the sorbent module contains zirconium oxide,wherein the one or more patient parameters include at least one from agroup consisting of: patient weight, patient volume, patient residualkidney function, an average number of dialysis sessions per week, and anaverage dialysis session length; and wherein the one or more dialysissession parameters include at least one from a group consisting of:dialysate flow rate, blood flow rate, dialyzer size, dialyzer type,dialysis time, ultrafiltration rate, a potassium, calcium, magnesium,and bicarbonate dialysis prescription, whether ammonia breakthroughoccurred, whether a pH alarm occurred, fluid removed during a session,total volume treated, starting water quality, URR target, URR achieved,clearance, whether a blood leak occurred, and whether a hypotensiveepisode occurred.
 14. The system of claim 9, wherein: the sorbent modulecontains zirconium phosphate, and wherein the control system sets thevolume and/or concentration of the one or more recharge solutions basedon a total cation and total CO₂ pumped through the sorbent module duringa prior dialysis session; or wherein the sorbent module containszirconium oxide, and wherein the control system sets the volume and/orconcentration of the one or more recharge solutions based on a totalphosphate pumped through the sorbent module during a prior dialysissession.